RL3127 | 108979-32-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: RL3127
• 英文别名: 2-chloro-2',4'-dimethoxy-trans-chalcone；2-Chlor-2',4'-dimethoxy-trans-chalkon；(2E)-3-(2-chlorophenyl)-1-(2,4-dimethoxyphenyl)prop-2-en-1-one；(E)-3-(2-chlorophenyl)-1-(2,4-dimethoxyphenyl)prop-2-en-1-one
• CAS: 108979-32-4
• 化学式: C₁₇H₁₅ClO₃
• 分子量: 302.757
• InChiKey: MVTVRJYQEXYLJX-JXMROGBWSA-N

物化性质

• 熔点：
  119-120 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  473.4±45.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯苯甲醛 、 2,4-二甲氧基苯乙酮 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以77%的产率得到RL3127
  参考文献：
  名称：

  Antiproliferative activity of chalcones with basic functionalities

  摘要：

  A library of chalcones with different basic groups were synthesized and evaluated for antiproliferative activities against the human breast cancer (MCF 7) and colon cancer (HCT 116) cell lines. Structure-activity relationships were analyzed by projection methods (PCA/PLS) and multiple linear regression. Polar volume, hydrogen bonding features, HOMO energies, and charge on the carbon were found to be important factors. A basic group on either ring A or B of the chalcone led to a favourable increase in polar Volume, but when present on ring B, it increased HOMO energies and decreased the positive charge on the carbon, both of which led to lower activity. Several examples showed that final activity of the chalcone was influenced by compensatory interactions among these parameters. In general, a single basic group on ring A was associated with good activity. A notable exception was compound 1-123 which had basic groups on both rings A and B but Still maintained a good activity profile with IC50 < 10 PM and selectivity ratios >2.5. There was some evidence to show that structural differences in chalcones influenced not only activity but mechanism of action. Compounds 6-130 and 7-140 which had basic groups on ring A interfered with cell cycle progression, but the dibasic chalcone 1-123 had no effect. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.042

文献信息

• Antiproliferative properties of piperidinylchalcones
  作者：Xiaoling Liu、Mei-Lin Go

  DOI：10.1016/j.bmc.2005.08.006

  日期：2006.1

  Methoxylated chalcones bearing N-methylpiperidinyl substituents oil ring A inhibited the growth of human tumour cell lines (MCF, HCT 116, and Jurkat) at IC50 values or < 5 mu M. Investigations oil a representative member (12) showed that antiproliferative activity was linked to the disruption of the cell cycle at G1 and G2/M phases. The effect was concentration dependent and was evident at the approximate IC50 of 12. Down regulation of cell cycle regulatory components (CDK4, cyclin B, E2F, and phosphorylated Rb) were observed under similar conditions. Methoxylated chalconcs without the piperidinyl substituent were found to exert equally potent and selective antiproliferative activity against HCT 116 tumour cells but did not interfere with cell cycle progression at their IC50 concentrations. The presence of the piperidinyl substituent in the chalcone template is proposed to lend specificity to the mechanism of antiproliferative activity, in addition to promoting a more desirable physicochemical profile. (c) 2005 Elsevier Ltd. All rights reserved.
• Antimitotic and Antiproliferative Activities of Chalcones: Forward Structure–Activity Relationship
  作者：Ahcène Boumendjel、Julien Boccard、Pierre-Alain Carrupt、Edwige Nicolle、Madeleine Blanc、Annabelle Geze、Luc Choisnard、Denis Wouessidjewe、Eva-Laure Matera、Charles Dumontet

  DOI：10.1021/jm0708331

  日期：2008.4.1

  A series of 59 chalcones was prepared and evaluated for the antimitotic effect against K562 leukemia cells. The most active chalcones were evaluated for their antiproliferative activity against a panel of I I human and murine cell cancer lines. We found that three chalcones were of great interest as potential antimitotic drugs. In vivo safety studies conducted on one of the most active chalcones revealed that the compound was safe, allowing further in vivo antitumor evaluation.
• Antiproliferative activity of chalcones with basic functionalities
  作者：Xiaoling Liu、Mei-Lin Go

  DOI：10.1016/j.bmc.2007.07.042

  日期：2007.11

  A library of chalcones with different basic groups were synthesized and evaluated for antiproliferative activities against the human breast cancer (MCF 7) and colon cancer (HCT 116) cell lines. Structure-activity relationships were analyzed by projection methods (PCA/PLS) and multiple linear regression. Polar volume, hydrogen bonding features, HOMO energies, and charge on the carbon were found to be important factors. A basic group on either ring A or B of the chalcone led to a favourable increase in polar Volume, but when present on ring B, it increased HOMO energies and decreased the positive charge on the carbon, both of which led to lower activity. Several examples showed that final activity of the chalcone was influenced by compensatory interactions among these parameters. In general, a single basic group on ring A was associated with good activity. A notable exception was compound 1-123 which had basic groups on both rings A and B but Still maintained a good activity profile with IC50 < 10 PM and selectivity ratios >2.5. There was some evidence to show that structural differences in chalcones influenced not only activity but mechanism of action. Compounds 6-130 and 7-140 which had basic groups on ring A interfered with cell cycle progression, but the dibasic chalcone 1-123 had no effect. (C) 2007 Elsevier Ltd. All rights reserved.
• Vallotton, 1923, vol. 3, p. 145,146
  作者：Vallotton

  DOI：——

  日期：——
• Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein
  作者：Kapil Juvale、Veronika F.S. Pape、Michael Wiese

  DOI：10.1016/j.bmc.2011.10.074

  日期：2012.1

  Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the current study was to investigate different multi-substituted chalcones for their BCRP inhibition. We synthesized chalcones and benzochalcones with different substituents (viz. OH, OCH3, Cl) on ring A and B of the chalcone structure. All synthesized compounds were tested by Hoechst 33342 accumulation assay to determine inhibitory activity in MCF-7 MX and MDCK cells expressing BCRP. The compounds were also screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity in the calcein AM accumulation assay and were found to be selective towards inhibition of BCRP. Substituents at position 20 and 40 on chalcone ring A were found to be essential for activity; additionally there was a great influence of substituents on ring B. Presence of 3,4-dimethoxy substitution on ring B was found to be optimal, while presence of 2- and 4-chloro substitution also showed a positive effect on BCRP inhibition. (C) 2011 Elsevier Ltd. All rights reserved.